Hodgkin's lymphoma symptoms and treatment

The most common presenting symptom for Hodgkin’s lymphoma is painless lymph node enlargement, most frequently involving nodes on the neck. More generalised lymph node enlargement is also common, but systemic spread to the liver, lungs, bone marrow and other organs is usually a late event.

Although localised disease usually occurs in lymph nodes above the diaphragm, isolated infradiaphragmatic disease may occur, and tends to be more common with the lymphocytepre dominant type.

Characteristic systemic symptoms, known as ‘B’symptoms, are unexplained fevers, drenching night sweats, and weight loss of >10% of total body weight. Presence of these symptoms is an adverse prognostic factor.

Other characteristic symptoms of Hodgkin's lymphoma, although less clearly associated with poor prognosis, are fatigue, generalised pruritus, and alcohol-induced pain in affected lymph nodes.

The lymphatic spread of Hodgkin’s lymphoma usually occurs in a step-wise fashion to contiguous lymph nodes. Anatomical staging, based on the Ann Arbor system ( Table 5.11), has largely determined treatment decisions. The suffix ‘B’ is added to the stage category for patients with systemic symptoms (i.e. fever, night sweats and weight loss), while patients without systemic symptoms are designated ‘A’.

Although stage and constitutional systems are still important factors, other prognostic factors have refined treatment decisions, which are now rarely based on anatomical stage only.

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For patients with early stage (I and IIA) Hodgkin's Lymphoma, prognostic groups are based on histological subtype, age, sex, number of sites of disease, the presence of bulky disease in the mediastinum and presence or absence of consititutional (B) symptoms. An example, as described by the EORTC, is shown in Table 5.22.

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For patients with advanced stage (IIB-IVB) Hodgkin's Lymphoma, the International Prognostic Factors Project has been developed 3. This is summarised in Table 5.33 and Figure 5.13.

For patients with none of the adverse factors, five-year failure free survival (FFS) was 84%. The presence of each factor reduces the five-year FFS by about 8%. This model forms a basis for risk-stratified treatment of advanced stage Hodgkin’s lymphoma in clinical trials.

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Major advances in the understanding of the possible causes and treatment of Hodgkin’s lymphoma in recent years have led to large reductions in mortality. The outlook for the majority of patients with Hodgkin's Lymphoma is now very good.

In addition, the recognition of the long-term side-effects of the original chemotherapy and radiotherapy regimens used for Hodgkin’s lymphoma have resulted in the development of new approaches with a lower incidence of long-term effects such as infertility and the development of second malignancy. This represents a major advance in a disease for which many life-years can potentially be lost by premature death as a result of treatment toxicity.

The use of extended field radiotherapy and/or alkylating agent-based chemotherapy, e.g. MOPP (mustine, vincristine procarbazine, prednisone), has resulted in high long- term disease free - and overall - survival rates for patients with Hodgkin’s lymphoma 4, 5. However, it is now recognised that each of these treatments is associated with significant long-term toxicity - of major importance in a disease which mainly affects young adults 6, 7.

The use of radiotherapy, particularly to the mediastinum, produces an increased risk of second malignancies such as lung and breast cancer, pulmonary fibrosis, and coronary heart disease 8-11. The use of alkylating agent-based chemotherapy increases the risks of secondary leukaemia, non-Hodgkin lymphoma, infertility, and premature ovarian failure 12-15.

A major emphasis of recent trials in Hodgkin’s lymphoma has therefore been to reduce radiation fields, and to introduce alternative chemotherapy regimens containing fewer alkylating agents.

At present, Ann Arbor stage 16, is still a major determinant of therapy, although risk stratification according to the factors mentioned above is used increasingly in clinical trial design, and routine practice.

Combined modality treatment with short duration chemotherapy followed by involved field radiotherapy is the approach taken for most patients.

Evidence from clinical trials shows that the use of brief duration combination chemotherapy such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), with limited (involved field) radiotherapy produces good long-term overall Hodgkin's Lymphoma survival rates of 70% and 90%, with less potential for long-term toxicity 17 than the previous approach using extended field radiotherapy alone 18.

The emphasis for current clinical trials is to determine whether therapy may be reduced further without compromising Hodgkin's lymphoma cure rates, perhaps using newer imaging techniques such as Positron-Emission Tomography (PET) scanning to determine responses at an early stage.

Combination chemotherapy is the primary modality of treatment for advanced Hodgkin’s lymphoma.

Involved field irradiation is often used to treat residual masses at the completion of systemic treatment 16, although it does not seem useful for patients in whom complete remission is achieved. 17 ABVD is now recognised as the standard regimen for advanced Hodgkin’s lymphoma, producing five-year failure free survival rates of 65-80 %, depending on the selection of patients 21, 22.

Recent studies of the use of more dose intensive regimens such as BEACOPP 23, 24used in conjunction with involved field radiotherapy, have produced five-year overall Hodgkin's Lymphoma survival rates of up to 90%, albeit with a high risk of permanent infertility and some risk of secondary acute leukaemia 23. These regimens are now being compared with standard therapy in randomized clinical trials.

In addition to the chemotherapy regimens described above, recent advances in the understanding of Hodgkin’s lymphoma at the cellular and molecular level have resulted in new antibody-based approaches being developed, including the use of immunotoxins. These are mostly directed at the CD30 antigen, expressed on RS cells 27, 28.

Clinical trials are in progress to test the efficacy of such antibodies against recurrent disease 29, 30.